Gangliosides appear to be important recognition molecules on the cell surface. Tetanus toxin binds to neuronal membranes. The binding components were identified by separating the membrane components by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After transferring the components to nitrocellulose sheets, the transfers were overlayed with iodinated toxin. Toxin only bound to the region where lipids migrate. The lipids were separated by thin-layer silica gel chromatography and the chromatograms overlayed with labeled toxin. The toxin bound to specific gangliosides identified as GT1b and GD1b. Thus, gangliosides appear to be the specific receptors for tetanus toxin in neuronal membranes. Kidney epithelial cells form tight intercellular junctions in culture with well-separated apical and basolateral plasma membranes. Exogenous gangliosides taken up by the apical membrane were unable to pass through the tight junctions to the basolateral surface. The kidney cells have a hormone regulated active sodium transport system. The hormone receptors, adenylate cyclase and Na+, K+ ATPase are located in the basolateral membrane whereas the sodium channels are in the apical membrane. When gangliosides were incorporated into the apical surface, hormone-stimulated transport was enhanced. Transport is also stimulated by 8-bromo-cyclic AMP and cholera toxin which increases intracellular cyclic AMP. Ganglioside insertion also increased transport mediated by either agent. The effect of gangliosides on sodium transport was specific as GD1a and GM1 were stimulatory whereas GM3 a less complex ganglioside had no effect. These results implicate gangliosides as cell surface modulators of sodium channels.